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Article ; Online: Natural polyphenolic coffee extract administration relieves chronic nociplastic pain in a reserpine-induced fibromyalgia-like female mouse model.

Toledano-Martos, Rubén / Bagó-Mas, Anna / Deulofeu, Meritxell / Homs, Judit / Fiol, Núria / Verdú, Enrique / Boadas-Vaello, Pere

Brain and behavior

2024 Volume 14, Issue 1, Page(s) e3386

Abstract: Introduction: Nociplastic pain involves reflexive and nonreflexive pain responses and it is a core symptom of fibromyalgia (FM). The increasing prevalence of this health condition and the low rates of patients' quality of life, combined with the lack of ...

Abstract	Introduction: Nociplastic pain involves reflexive and nonreflexive pain responses and it is a core symptom of fibromyalgia (FM). The increasing prevalence of this health condition and the low rates of patients' quality of life, combined with the lack of suitable pharmacologic treatments, evidence the demand to research new alternatives. Polyphenols may be potential therapeutic candidates as they have been reported to exert pathological pain modulation in preclinical models. In that context, this work was aimed to study the antinociceptive effects of a polyphenolic extract obtained from decaffeinated ground roasted coffee, in the RIM6 FM-like mouse model. Methods: To this end, RIM6 adult ICR-CD1 female mice were administered daily once a week with either 10 or 15 mg/kg of extract, and reflexive pain responses were evaluated for up to 3 weeks. At the end, the depressive-like behavior was assessed as a nonreflexive pain response, and spinal cord and serum samples were collected for immunohistochemical and toxicological analyses. Results: These findings showed that the repeated administration of the coffee polyphenolic extract (CE) modulated reflexive pain responses, depressive-like behavior, and spinal cord gliosis in a dose-dependent manner, without signs of systemic toxicity. Conclusion: Thus, the CE may be a potential pharmacological treatment suitable to relieve nociplastic pain responses characteristic of FM.
MeSH term(s)	Humans ; Female ; Mice ; Animals ; Fibromyalgia/drug therapy ; Fibromyalgia/chemically induced ; Reserpine/adverse effects ; Hyperalgesia/drug therapy ; Quality of Life ; Mice, Inbred ICR ; Chronic Pain
Chemical Substances	Reserpine (8B1QWR724A)
Language	English
Publishing date	2024-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2623587-0
ISSN	2162-3279 ; 2162-3279
ISSN (online)	2162-3279
ISSN	2162-3279
DOI	10.1002/brb3.3386
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Central Neuropathic Pain Development Modulation Using Coffee Extract Major Polyphenolic Compounds in Spinal-Cord-Injured Female Mice.

Soler-Martínez, Roger / Deulofeu, Meritxell / Bagó-Mas, Anna / Dubový, Petr / Verdú, Enrique / Fiol, Núria / Boadas-Vaello, Pere

Biology

2022 Volume 11, Issue 11

Abstract: It was recently shown that coffee polyphenolic extract exerts preventive effects on central neuropathic pain development, but it is unknown whether its beneficial effects are associated with only one of its major polyphenolic compounds or if the whole ... ...

Abstract	It was recently shown that coffee polyphenolic extract exerts preventive effects on central neuropathic pain development, but it is unknown whether its beneficial effects are associated with only one of its major polyphenolic compounds or if the whole extract is needed to exert such effects. The main objective of this study was to determine whether the separate administration of major polyphenols from coffee extract exerts preventive effects on the development of central neuropathic pain in mice compared with the effects of the whole coffee extract. Thus, spinal-cord-injured female ICR-CD1 mice were daily treated with either coffee extract or its major polyphenolic compounds during the first week, and reflexive and nonreflexive pain responses were evaluated within the acute phase of spinal cord injury. In addition, the injury-induced gliosis and dorsal horn sprouting were evaluated with immunohistochemistry. The results showed that the coffee extract prevented spinal cord injury-induced neuropathic pain, whereas its major polyphenolic compounds resulted in reflexive pain response attenuation. Both preventive and attenuation effects were associated with gliosis and afferent fiber sprouting modulation. Overall, the results suggested that coffee extract effects may be associated with potential synergistic mechanisms exerted by its major polyphenolic compounds and not by the sole effect of only one of them.
Language	English
Publishing date	2022-11-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology11111617
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Article ; Online: Long-Lasting Nociplastic Pain Modulation by Repeated Administration of Sigma-1 Receptor Antagonist BD1063 in Fibromyalgia-like Mouse Models.

Álvarez-Pérez, Beltrán / Bagó-Mas, Anna / Deulofeu, Meritxell / Vela, José Miguel / Merlos, Manuel / Verdú, Enrique / Boadas-Vaello, Pere

International journal of molecular sciences

2022 Volume 23, Issue 19

Abstract: Sigma-1 receptor (σ1R) ligands have been shown to be effective at relieving neuropathic and inflammatory pain, but have not yet been tested in experimental models of fibromyalgia. The objective of this study was to evaluate the effect of a σ1R antagonist ...

Abstract	Sigma-1 receptor (σ1R) ligands have been shown to be effective at relieving neuropathic and inflammatory pain, but have not yet been tested in experimental models of fibromyalgia. The objective of this study was to evaluate the effect of a σ1R antagonist (BD1063) compared to pregabalin. ICR-CD1 female mice were subjected to either six repeated injections of reserpine, to cause reserpine-induced myalgia (RIM6), or acidified saline intramuscular injections (ASI). In these two models, we evaluated the effect of BD1063 and pregabalin on thermal hypersensitivity, anxiety-like and depression-like behaviors, and on spinal cord gliosis. BD1063 exerted an antinociceptive effect on both reflexive (thermal hyperalgesia) and nonreflexive (anxiety- and depression-like) pain behaviors, and reduced spinal astroglial and microglial reactivity, following repeated treatment for 2 weeks. Interestingly, the effects of BD1063 were long-term, lasting several weeks after treatment discontinuation in both fibromyalgia-like models. Similar results were obtained with pregabalin, but the effects on pain behaviors lasted for a shorter length of time, and pregabalin did not significantly modulate spinal glial reactivity. The inhibitory and long-lasting effect of pharmacological blockade of σ1Rs on both sensory and affective dimensions of nociplastic-like pain and spinal cord gliosis in two experimental models of fibromyalgia support the application of this therapeutic strategy to treat fibromyalgia.
MeSH term(s)	Analgesics/therapeutic use ; Animals ; Chronic Pain/drug therapy ; Disease Models, Animal ; Female ; Fibromyalgia/drug therapy ; Gliosis ; Hyperalgesia/drug therapy ; Mice ; Mice, Inbred ICR ; Pregabalin/therapeutic use ; Receptors, sigma/antagonists & inhibitors ; Reserpine/adverse effects ; Sigma-1 Receptor
Chemical Substances	Analgesics ; Receptors, sigma ; Pregabalin (55JG375S6M) ; Reserpine (8B1QWR724A)
Language	English
Publishing date	2022-10-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms231911933
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Article ; Online: Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition.

Álvarez-Pérez, Beltrán / Deulofeu, Meritxell / Homs, Judit / Merlos, Manuel / Vela, José Miguel / Verdú, Enrique / Boadas-Vaello, Pere

Scientific reports

2022 Volume 12, Issue 1, Page(s) 9719

Abstract: Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective ... ...

Abstract	Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5-6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6.
MeSH term(s)	Animals ; Chronic Pain/drug therapy ; Disease Models, Animal ; Fibromyalgia/drug therapy ; Mice ; Pregabalin/pharmacology ; Pregabalin/therapeutic use ; Reserpine/pharmacology
Chemical Substances	Pregabalin (55JG375S6M) ; Reserpine (8B1QWR724A)
Language	English
Publishing date	2022-06-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-13968-7
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Article ; Online: Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice.

Bagó-Mas, Anna / Korimová, Andrea / Deulofeu, Meritxell / Verdú, Enrique / Fiol, Núria / Svobodová, Viktorie / Dubový, Petr / Boadas-Vaello, Pere

Scientific reports

2022 Volume 12, Issue 1, Page(s) 14980

Abstract: More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive effects, the ...

Abstract	More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive effects, the present work aimed to study preventive effects on SCI-induced CNP development by repeated administration of two vegetal polyphenolic extracts: grape stalk extract (GSE) and coffee extract (CE). Thermal hyperalgesia and mechanical allodynia were evaluated at 7, 14 and 21 days postinjury. Then, gliosis, ERK phosphorylation and the expression of CCL2 and CX3CL1 chemokines and their receptors, CCR2 and CX3CR1, were analyzed in the spinal cord. Gliosis and CX3CL1/CX3CR1 expression were also analyzed in the anterior cingulate cortex (ACC) and periaqueductal gray matter (PAG) since they are supraspinal structures involved in pain perception and modulation. GSE and CE treatments modulated pain behaviors accompanied by reduced gliosis in the spinal cord and both treatments modulated neuron-glia crosstalk-related biomolecules expression. Moreover, both extracts attenuated astrogliosis in the ACC and PAG as well as microgliosis in the ACC with an increased M2 subpopulation of microglial cells in the PAG. Finally, GSE and CE prevented CX3CL1/CX3CR1 upregulation in the PAG, and modulated their expression in ACC. These findings suggest that repeated administrations of either GSE or CE after SCI may be suitable pharmacologic strategies to attenuate SCI-induced CNP development by means of spinal and supraspinal neuroinflammation modulation.
MeSH term(s)	Animals ; Disease Models, Animal ; Female ; Gliosis/complications ; Gliosis/etiology ; Hyperalgesia/complications ; Hyperalgesia/etiology ; Mice ; Mice, Inbred ICR ; Neuralgia/complications ; Neuralgia/etiology ; Spinal Cord/metabolism ; Spinal Cord Injuries/complications ; Spinal Cord Injuries/drug therapy ; Spinal Cord Injuries/metabolism ; Vitis
Language	English
Publishing date	2022-09-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-19109-4
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Article ; Online: Central Neuropathic Pain Development Modulation Using Coffee Extract Major Polyphenolic Compounds in Spinal-Cord-Injured Female Mice

Roger Soler-Martínez / Meritxell Deulofeu / Anna Bagó-Mas / Petr Dubový / Enrique Verdú / Núria Fiol / Pere Boadas-Vaello

Biology, Vol 11, Iss 1617, p

2022 Volume 1617

Abstract	It was recently shown that coffee polyphenolic extract exerts preventive effects on central neuropathic pain development, but it is unknown whether its beneficial effects are associated with only one of its major polyphenolic compounds or if the whole extract is needed to exert such effects. The main objective of this study was to determine whether the separate administration of major polyphenols from coffee extract exerts preventive effects on the development of central neuropathic pain in mice compared with the effects of the whole coffee extract. Thus, spinal-cord-injured female ICR-CD1 mice were daily treated with either coffee extract or its major polyphenolic compounds during the first week, and reflexive and nonreflexive pain responses were evaluated within the acute phase of spinal cord injury. In addition, the injury-induced gliosis and dorsal horn sprouting were evaluated with immunohistochemistry. The results showed that the coffee extract prevented spinal cord injury-induced neuropathic pain, whereas its major polyphenolic compounds resulted in reflexive pain response attenuation. Both preventive and attenuation effects were associated with gliosis and afferent fiber sprouting modulation. Overall, the results suggested that coffee extract effects may be associated with potential synergistic mechanisms exerted by its major polyphenolic compounds and not by the sole effect of only one of them.
Keywords	neuropathic pain ; spinal cord injury ; polyphenols ; coffee extract ; chlorogenic acid ; neochlorogenic acid ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-lasting reflexive and nonreflexive pain responses in two mouse models of fibromyalgia-like condition

Beltrán Álvarez-Pérez / Meritxell Deulofeu / Judit Homs / Manuel Merlos / José Miguel Vela / Enrique Verdú / Pere Boadas-Vaello

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 15

Abstract: Abstract Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of ... ...

Abstract	Abstract Nociplastic pain arises from altered nociception despite no clear evidence of tissue or somatosensory system damage, and fibromyalgia syndrome can be highlighted as a prototype of this chronic pain subtype. Currently, there is a lack of effective treatments to alleviate both reflexive and nonreflexive pain responses associated with fibromyalgia condition, and suitable preclinical models are needed to assess new pharmacological strategies. In this context, although in recent years some remarkable animal models have been developed to mimic the main characteristics of human fibromyalgia, most of them show pain responses in the short term. Considering the chronicity of this condition, the present work aimed to develop two mouse models showing long-lasting reflexive and nonreflexive pain responses after several reserpine (RIM) or intramuscular acid saline solution (ASI) injections. To our knowledge, this is the first study showing that RIM6 and ASI mouse models show reflexive and nonreflexive responses up to 5–6 weeks, accompanied by either astro- or microgliosis in the spinal cord as pivotal physiopathology processes related to such condition development. In addition, acute treatment with pregabalin resulted in reflexive pain response alleviation in both the RIM6 and ASI models. Consequently, both may be considered suitable experimental models of fibromyalgia-like condition, especially RIM6.
Keywords	Medicine ; R ; Science ; Q
Subject code	501
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice

Anna Bagó-Mas / Andrea Korimová / Meritxell Deulofeu / Enrique Verdú / Núria Fiol / Viktorie Svobodová / Petr Dubový / Pere Boadas-Vaello

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 21

Abstract: Abstract More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive ... ...

Abstract	Abstract More than half of spinal cord injury (SCI) patients develop central neuropathic pain (CNP), which is largely refractory to current treatments. Considering the preclinical evidence showing that polyphenolic compounds may exert antinociceptive effects, the present work aimed to study preventive effects on SCI-induced CNP development by repeated administration of two vegetal polyphenolic extracts: grape stalk extract (GSE) and coffee extract (CE). Thermal hyperalgesia and mechanical allodynia were evaluated at 7, 14 and 21 days postinjury. Then, gliosis, ERK phosphorylation and the expression of CCL2 and CX3CL1 chemokines and their receptors, CCR2 and CX3CR1, were analyzed in the spinal cord. Gliosis and CX3CL1/CX3CR1 expression were also analyzed in the anterior cingulate cortex (ACC) and periaqueductal gray matter (PAG) since they are supraspinal structures involved in pain perception and modulation. GSE and CE treatments modulated pain behaviors accompanied by reduced gliosis in the spinal cord and both treatments modulated neuron-glia crosstalk-related biomolecules expression. Moreover, both extracts attenuated astrogliosis in the ACC and PAG as well as microgliosis in the ACC with an increased M2 subpopulation of microglial cells in the PAG. Finally, GSE and CE prevented CX3CL1/CX3CR1 upregulation in the PAG, and modulated their expression in ACC. These findings suggest that repeated administrations of either GSE or CE after SCI may be suitable pharmacologic strategies to attenuate SCI-induced CNP development by means of spinal and supraspinal neuroinflammation modulation.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Artificial Neural Networks Coupled with MALDI-TOF MS Serum Fingerprinting To Classify and Diagnose Pathological Pain Subtypes in Preclinical Models.

Deulofeu, Meritxell / Peña-Méndez, Eladia M / Vaňhara, Petr / Havel, Josef / Moráň, Lukáš / Pečinka, Lukáš / Bagó-Mas, Anna / Verdú, Enrique / Salvadó, Victoria / Boadas-Vaello, Pere

ACS chemical neuroscience

2022 Volume 14, Issue 2, Page(s) 300–311

Abstract: Pathological pain subtypes can be classified as either neuropathic pain, caused by a somatosensory nervous system lesion or disease, or nociplastic pain, which develops without evidence of somatosensory system damage. Since there is no gold standard for ... ...

Abstract	Pathological pain subtypes can be classified as either neuropathic pain, caused by a somatosensory nervous system lesion or disease, or nociplastic pain, which develops without evidence of somatosensory system damage. Since there is no gold standard for the diagnosis of pathological pain subtypes, the proper classification of individual patients is currently an unmet challenge for clinicians. While the determination of specific biomarkers for each condition by current biochemical techniques is a complex task, the use of multimolecular techniques, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), combined with artificial intelligence allows specific fingerprints for pathological pain-subtypes to be obtained, which may be useful for diagnosis. We analyzed whether the information provided by the mass spectra of serum samples of four experimental models of neuropathic and nociplastic pain combined with their functional pain outcomes could enable pathological pain subtype classification by artificial neural networks. As a result, a simple and innovative clinical decision support method has been developed that combines MALDI-TOF MS serum spectra and pain evaluation with its subsequent data analysis by artificial neural networks and allows the identification and classification of pathological pain subtypes in experimental models with a high level of specificity.
MeSH term(s)	Humans ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Artificial Intelligence ; Neural Networks, Computer ; Pain/diagnosis
Language	English
Publishing date	2022-12-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.2c00665
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Article ; Online: Evaluation of the New Beckmann Coulter Analyzer DxH 900 Compared to Sysmex XN20

Maite Serrando Querol / Javier Nieto-Moragas / Anna Marull Arnall / Meritxell Deulofeu Figueras / Orlando Jiménez-Romero

Diagnostics, Vol 11, Iss 1756, p

Analytical Performance and Flagging Efficiency

2021 Volume 1756

Abstract: Efficiency and accuracy in automated hematology analyzers are very important for clinical laboratories. The purpose was to evaluate the flags and results reported by the newest Beckman Coulter analyzer DxH 900 compared to the Sysmex XN20 system. Samples ... ...

Abstract	Efficiency and accuracy in automated hematology analyzers are very important for clinical laboratories. The purpose was to evaluate the flags and results reported by the newest Beckman Coulter analyzer DxH 900 compared to the Sysmex XN20 system. Samples were analyzed on the XN20 (Sysmex, Kobe, Japan) and on the Beckman Coulter DxH 900 (Beckman Coulter, Miami, Florida, USA). Slide reviews were performed microscopically. Morphologic criteria were used to identify abnormal cells as recommended by International Consensus Group for Hematology (ICSH): blasts, immature granulocytes (IG%), abnormal lymphocytes (ALs) and plasma cells. Results: there was a strong correlation between the analyzers in almost all clinical parameters tested. Both DxH 900 and XN20 showed an excellent degree of association for the leukocyte differential compared to the reference method (manual microscopy). When it comes to IG%, XN20 showed a positive bias for higher results. Related to platelets, there are no differences between the two methods for PLT count. For mean platelet volume (MPV), DxH 900 provided 100% results of the samples analyzed while XN20 while in the XN20 analyzer, 16% of the results were missing. From our results we came to the conclusion that both analyzers, DxH 900 and XN20 were clinically accurate and efficient. Abnormal Lymphocyte detection highlighted the differences between the two technologies as only minimal agreement was obtained. DxH 900 demonstrated higher sensitivity in detecting IG with good correlation with microscopic review. The DxH 900 for platelet clumps identification provides an excellent flag (PLT Clumps) with the highest sensitivity observed in our evaluation.
Keywords	cell blood count (CBC) ; leukocyte differential ; Beckman Coulter DxH 900 ; Sysmex XN20 ; Medicine (General) ; R5-920
Subject code	630
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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